S167: EFFICACY AND SAFETY OF LUSPATERCEPT FOR THE TREATMENT OF ANEMIA IN PATIENTS WITH MYELOFIBROSIS: RESULTS FROM THE ACE-536-MF-001 STUDY
Authors: Aaron T. Gerds, Claire Harrison, Jean-Jacques Kiladjian, Ruben Mesa, Alessandro Vannucchi, Rami S. Komrokji, Prithviraj Bose, Marina Kremyanskaya, Adam Mead, Jason Gotlib, Fabian Sanabria, Niloufar Marsousi, Ana Carolina Giuseppi, Huijing Jiang, Jeanne Palmer, Kelly Mccaul, Vincent Ribrag, Srdan Verstovsek, Francesco Passamonti
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Many patients (pts) with myelofibrosis (MF) experience anemia due to disease or JAK inhibitor (JAKi) therapy. Aims: To assess the final efficacy and safety results from the open-label, phase 2 ACE-536-MF-001 study (NCT03194542) of luspatercept (LUSPA) for the treatment of transfusion-dependent (TD) or independent anemia in pts with MF. Methods: Eligible pts comprised 4 cohorts (coh) based on TD (defined as receiving 4–12 red blood cell (RBC) units/84 days up to C1D1) and stable ruxolitinib (RUX) treatment; coh 1: no TD, no RUX; coh 2: TD, no RUX; coh 3A: no TD, RUX; coh 3B: TD, RUX. Pts received subcutaneous LUSPA 1.0 mg/kg (1.33 mg/kg for pts in coh 3B expansion) with titration up to 1.75 mg/kg in 21-day cycles. Anemia response was assessed at day 169 and treatment was extended for pts showing clinical benefit; pts were followed for ≥3 years post last dose. The primary endpoint was anemia response over 84 consecutive days (defined as ≥1.5 g/dL hemoglobin [Hgb] from baseline [coh 1/3A] or RBC transfusion-free [coh 2/3B]); secondary endpoints included duration of anemia response (DOR), transfusion frequency, changes in Hgb level, symptom response, and safety. Results: Of 95 pts in the intent-to-treat (ITT) group, 28 discontinued at day 169 due to lack of clinical benefit. Median (range) age was 71.0 (50–89) years. Most (54.7%) pts had primary MF, intermediate-2 risk score (75.8%), and >2 years since initial diagnosis (74.7%). Median prior RUX therapy was 18.1 months (coh 3A/3B); 84.7% of pts had baseline transfusion burden 6–12 units/84 days (coh 2/3B). Mean treatment duration was 42.8 weeks. In coh 3B, 26.3% of pts achieved transfusion independence during the primary treatment period vs 9.5% in coh 2; in coh 1 and 3A, 13.6% and 14.3% pts had a Hgb increase of >1.5g/dL, respectively (Table). During the entire treatment period, 31.6% of pts in coh 3B achieved transfusion independence vs 19.0% in coh 2; in coh 1 and coh 3A, 18.2% and 21.4% of pts had a Hgb increase of ≥1.5 g/dL, respectively. TD pts had a median (range) DOR of 448.0 days (85–1582) in coh 3B, and a mean of 623.0 days (602–644) in coh 2. Median (range) DOR in pts with anemia only was 126.0 days (84–1163) in coh 1, and 88.5 days (84–93) in coh 3A. During the primary treatment period, transfusion burden was reduced by ≥50% in 50.0% pts in coh 3B and 47.6% pts in coh 2. Throughout the entire treatment period, 21.1% pts achieved a mean Hgb increase ≥1.5 g/dL from baseline in coh 3B vs 14.3% in coh 2, 27.3% in coh 1, and 50.0% in coh 3A. A mean ≥50% reduction from baseline in symptom score was achieved by 15.8% pts in coh 3B, 9.5% in coh 2, 9.1% in coh 1, and 21.4% in coh 3A. Overall, 93.7% of pts had ≥1 treatment-emergent adverse event (TEAE; 47.4% treatment-related AE [TRAE], most commonly hypertension [17.9%]); 38.9% had ≥1 serious AE, 3.2% were treatment related. Nine TEAEs (1 TRAE) led to LUSPA discontinuation. Two (2.2%) pts had transformation to acute myeloid leukemia. Nine (9.5%) pts died on treatment; no deaths were considered related to the study drug. Summary/Conclusion: LUSPA resulted in transfusion independence in TD pts ± prior RUX exposure and durable anemia response in non-TD pts. LUSPA safety profile was acceptable in MF and consistent with previous studies. No new safety signals were identified. These results support continued study of LUSPA in MF-induced anemia in TD pts receiving JAKi in the phase 3 INDEPENDENCE study.Keywords: Myelofibrosis, Transfusion, Anemia